Uterine leiomyomas (fibroids) are the leading indication for hysterectomy in the United States. Despite the morbidity and high medical costs associated with fibroids, there has been little epidemiologic study of this condition in the United States. Uterine leiomyomas are histologically identifiable as benign smooth muscle tumors with varying amounts of associated fibrous tissue. Many women have more than one uterine leiomyoma, but each appears to be clonally distinct. MED12 mutations that appear to cause gain of function are found in the majority of tumors and are likely triggers for tumorigenesis. Several specific cytogenetic changes have also been identified in tumor tissue, but most tumors show no chromosomal abnormalities. These benign tumors are hormone-dependent. They develop after puberty and regress after menopause. Both estrogen and progesterone are considered important stimulants, or at least permissive factors for tumor growth. To address the research needs in this field we have designed four studies. The first, the NIEHS Uterine Fibroid Study, is a large epidemiologic study of black and white women, aged 35-49, in which the randomly selected participants were screened for fibroids with ultrasound. The second study (Fibroid Growth Study, Shyamal Peddada, PI) is a clinical study of fibroids designed to describe fibroid growth. The third study, Postpartum Uterine Regression, monitored fibroid change with pregnancy and postpartum uterine regression. The fourth study, is a prospective study of fibroid incidence and growth. We continue to analyze data from the NIEHS Uterine Fibroid Study. We are currently investigating alcohol exposure as a potential risk factor for fibroid development in this sample. We began enrolment in a prospective study of fibroids in November, 2010, and completed recruitment of nearly 1700 African American women, aged 23-34 by the end of 2012. Any prior diagnosis of fibroids was an exclusion criterion. The Study of Environment, Lifestyle & Fibroids (SELF) is based in the Detroit, Michigan area with collaboration from Henry Ford Health System. Participants are screened for fibroids with ultrasound at enrollment (detection limit of lesion = 0.5 cm diameter). There are three subsequent clinic visits at approximately 20-month intervals to monitor fibroids by ultrasound examinations in order to identify onset time. Those found to have fibroids at enrollment (newly detected, not previously clinically diagnosed), as well as those who develop fibroids during the study, will be followed in the same manner to assess development of additional new fibroids and to measure fibroid growth. We collected risk factor and symptom data at enrollment and are continuing to do so prospectively for five years. The study is designed to collect a broad spectrum of exposure data including recognized risk factors for fibroids (age of menarche, pregnancy history, alcohol use, body mass index) and potential risk factors for which there has been only suggestive data. Three primary hypotheses will be tested. (1) Vitamin D deficiency is a risk factor for fibroids, (2) Reproductive tract infections are risk factors for fibroids, and (3) A higher proportion of African ancestry is associated with increased fibroid risk (African ancestry measured by informative SNPs known to have very different frequencies between Europeans and Africans). We have completed data collection for the 2nd follow-up and are more than half finished with data collection for the 3rd and final follow-up visit. Enrollment activities included: orientation to study, pre-enrollment self-administered questionnaire, web-based questionnaire, food-frequency questionnaire, computer-assisted telephone interview, clinic visit with ultrasound. measure of blood pressure, weight, height, skin reflectance, specimen collection (blood, urine, vaginal swabs), menstrual cycle diary to prospectively record at least one menstrual cycle and bleeding pattern, and an early life questionnaire that the participant administers to her mother (if available). The enrollment data have been analyzed to examine the associations of the following exposures with prevalent fibroids: keloid scars, being fed soy formula as an infant, Depo Provera use, and reproductive tract infections. I also collaborate with Kathie Hartmann on the Right From the Start Study, a pregnancy study that screens participants for fibroids with ultrasound early in their pregnancies. with ultrasound early in their pregnancies.